RISCUL DE A DEZVOLTA UN ACCIDENT VASCULAR CEREBRAL CORELAT CU HTA ŞI HVS LA HIPERTENSIVUL VÂRSTNIC TRATAT CU ACEI ŞI BRA
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1 RISCUL DE A DEZVOLTA UN ACCIDENT VASCULAR CEREBRAL CORELAT CU HTA ŞI HVS LA HIPERTENSIVUL VÂRSTNIC TRATAT CU ACEI ŞI BRA MARIANA ADĂMUŢIU 1, IOAN MANIŢIU 2 1 Spitalul Judeţean de Urgenţă Alba Iulia, 2 Universitatea Lucian Blaga Sibiu Cuvinte cheie: hipertensiune, accident, ACEI, BRA, vârstnic Keywords: hypertension, cerebral vascular stroke, ACEI, BRA, elderly Rezumat: Pentru fiecare decadă de viaţă după 55 de ani, rata de apariţie a accidentelor vasculare cerebrale se dublează, mai mult de 80% din cazurile de accidente vasculare cerebrale apar după vârsta de 65 de ani. Hipertensiunea arterială este factorul de risc principal pentru toate tipurile de accidente vasculare cerebrale. Hipertrofia ventriculară stângă reprezintă un factor de risc crescut pentru morbiditatea şi mortalitatea prin afecţiuni cerebrovasculare. Numeroase studii (PROGRESS, SCOPE, LIFE, HYVET, SYST-EURO) arată că blocarea medicamentoasă a sistemului renină angiotensină este importantă pentru prevenirea accidentelor vasculare cerebrale. Tratamentul hipertensiunii arteriale previne dezvoltarea unui accident. Abstract: For each life decade that elapses after the age of 55, the rate of appearance of the cerebral vascular strokes doubles, more than 80% of the cases of cerebral vascular strokes appear after the age of 65. The high arterial pressure is the main risk factor for all types of cerebral vascular strokes. Left ventricular hypertrophy represents an increased risk factor in the case of morbidity and mortality through cerebral vascular illnesses. Numerous studies (PROGRESS, SCOPE, LIFE, HYVET, SYST- EURO) show that drug blocking of the rennin angiotensin system is important in order to prevent cerebral vascular strokes.(1-3) The treatment of the arterial hypertension prevents the development of a cerebral vascular stroke. Creierul reprezintă un organ ţintă afectat precoce de hipertensiune (4), factorul de risc major influenţabil pentru accidentul ischemic şi hemoragic.(5) Accidentul reprezintă a doua cauză de mortalitate pe plan mondial. Riscul creşte gradual cu valorile tensiunii arteriale. Riscul relativ de accident este multiplicat de patru ori la hipertensivi, pentru valori ale tensiunii arteriale superioare celei de 160/90 mm Hg. Studiul SHEP (Systolic Hypertension in the Elderly Program) a demonstrat că tratamentul hipertensiunii arteriale sistolice la subiecţii cu vârsta de 60 de ani şi peste reduce cu 36% incidenţa accidentelor vasculare cerebrale.(6) Afecţiunile ischemice, hemoragice şi degenerative cerebrale reprezintă o problemă majoră de sănătate, în particular la, determinând pierderea autonomiei acestora. După vârstă, hipertensiunea arterială reprezintă cel mai important factor de risc pentru leziunile substanţei albe cerebrale, ceea ce reprezintă un factor de prognostic important pentru accidentele vasculare cerebrale, tulburările cognitive, demenţa şi deces. Pacienţii hipertensivi prezintă o rată accelerată de dezvoltare a leziunilor substanţei albe comparativ cu cei normotensivi.(7,8) Accidentul este o cauză majoră de dizabilitate şi deces, iar incidenţa lui creşte linear odată cu vârsta şi cu valorile tensiunii arteriale.(9,10) Figura nr. 1. Corelaţia între reducerea tensiunii arteriale sistolice şi incidenţa accidentului Difference (reference minus experimental) in systolic pressure (mm Hg) Staessen et al. Lancet 2001; 358: Istoricul de hipertensiune arterială reprezintă cel mai important factor de risc pentru dezvoltarea unui accident, în special hemoragic.(11) 1 Autor corespondent: Mariana Adămuţiu, Bd. Revoluţiei 1989, Nr. 23, Cod , Alba Iulia, România, mariana_adamutiu@yahoo.com, Tel: Articol intrat în redacţie în şi acceptat spre publicare în ACTA MEDICA TRANSILVANICA Septembrie 2013;2(3): AMT, vol. II, nr. 3, 2013, pag. 160
2 Figura nr. 2. Tensiunea arterial şi mortalitatea prin accident Lancet 2002; 360: Factorii de risc implicaţi în dezvoltarea unui accident pot fi grupaţi în: 1. Neinfluenţabili - vârsta - sexul - greutatea mică la naştere - predispoziţia genetică 2. Influenţabili - hipertensiunea arterială - fibrilaţia atrială cronică - diabetul zaharat - dislipidemia - expunerea la fumul de ţigară - siclemia - sedentarismul - obezitatea 3. Potenţial influenţabili - consumul excesiv de alcool - abuzul de droguri - administrarea de contraceptive per os - tulburări ale somnului Hipertensiunea arterială rămâne cel mai important factor de risc influenţabil pentru dezvoltarea unui accident (12,13,14), iar tratarea acesteia reprezintă cea mai importantă strategie de prevenţie a instalării acestuia.(15) Tensiunea arterială crescută este un factor de risc independent pentru instalarea aterosclerozei carotidiene, ajutată fiind de vârstă, sex (masculin mai frecvent), statusul de fumător şi de nivelul colesterolului seric.(16,17) Valorile mari tensionale determină cu vremea, creşterea grosimii mediei arteriale, degenerare hialină, necroză fibrinoidă, îngustarea lumenului, formarea de microanevrisme la nivelul arterelor mici perforante şi a arteriolelor intraparenchimatoase cerebrale, concomitent cu o dezvoltare inadecvată a circulaţiei colaterale.(18,19) Reanaliza din 2009 a Ghidului European de management a hipertensiunii arteriale arată că dintr-un grup de 192 de pacienţi hipertensivi netrataţi, cu vârsta cuprinsă între 18 şi 90 de ani, fără a prezenta afecţiuni cardiovasculare decelabile, leziunile silenţioase cerebrovasculare (leziunile substanţei albe, infarcte lacunare, microhemoragii cerebrale) erau mai numeroase (44%) decât cele cardiace (25%) sau renale (26%).(20,21) Hipertrofia ventriculară stângă reprezintă un factor de risc independent pentru morbiditatea şi mortalitatea prin afecţiuni cardiovasculare la pacienţii hipertensivi. Bikkina şi colaboratorii (22) arată asocierea dintre masa ventriculului stâng şi riscul crescut pentru evenimente cerebrovasculare (accidente REFERATE AMT, vol. II, nr. 3, 2013, pag. 161 vasculare hemoragice, accidente ischemice tranzitorii) prezent la pacienţii cuprinşi în studiul Framingham. Se sugerează că patternul geometriei ventriculului stâng furnizează informaţii referitor la dezvoltarea afecţiunilor cardiovasculare (23) şi la prezenţa leziunilor de organ ţintă în hipertensiunea arterială.(24,25) Pacienţii cu hipertrofie ventriculară stângă concentrică dezvoltă leziuni de organ ţintă la nivel renal, retinian mai precoce decât cei cu altă geometrie a hipertrofiei ventriculare stângi (excentrică). Unele studii au găsit asocieri între hipertrofia ventriculară stângă şi leziunile substanţei albe cerebrale (25-30), altele nu.(31) S-a dovedit existenţa unei relaţii apropiate între leziunile silenţioase ale substanţei albe cerebrale şi hipertrofia ventriculară stângă la pacienţii cu hipertensiune arterială netratată.(29) Hipertensiunea arterială este considerată un factor de risc major pentru boala Alzheimer şi demenţa vasculară. Un control redus al valorilor tensiunii arteriale este asociat şi cu un declin al funcţiei cognitive.(32,33) Incidenţa accidentului (ischemic sau hemoragic) creşte după un accident ischemic tranzitor în prezenta hipertensiunii arteriale sau a altor factori de risc cardiovascular. Lewington subliniază legătura directă dintre incidenţa accidentului şi nivelul tensiunii arteriale sistolice şi diastolice pentru orice grup de vârstă, în special pentru.(10) O tensiune arterială matinală ridicată la un hipertensiv vârstnic este asociată cu un risc crescut de a dezvolta un accident, independent de valorile tensionale diurne sau nocturne.(34) Reducerea valorilor tensionale matinale reprezintă o nouă ţintă din punct de vedere terapeutic, în vederea prevenirii afectării precoce a organelor ţintă în boala hipertensivă. Sistemul renină angiotensină este implicat în menţinerea unui status hemodinamic normal. Autoreglarea circulaţiei cerebrale menţine un flux sanguin constant la nivelul creierului prin vasodilataţie când tensiunea arterială scade şi prin vasoconstricţie când tensiunea arterială creşte. Prin intermediul angiotensinei II are rol vasoconstrictor, modulând creşterea vasculară prin două tipuri de receptori cu funcţii opuse (AT1 şi AT2). Stimularea în exces a receptorilor AT1 determină mitogeneza în exces, cu reducerea complianţei vasculare, alterarea producerii de NO, creşterea reacţiei inflamatorii, toate acestea reprezentând reacţii caracteristice ale vaselor de sânge în hipertensiunea arterială. Blocarea receptorilor AT1 prin antagonişti ai receptorilor de angiotensină determină inversarea patologiei de mitoză şi inflamaţie, îmbunătăţeşte complianţa cerebrovasculară, ameliorând producerea de NO. Aceste efecte determină reducerea vulnerabilităţii creierului la ischemie, şi dacă are loc un accident protejează fluxul sanguin în zona de penumbră cu o reducere substanţială a injuriei neuronale.(35) Stimularea receptorilor AT2 antagonizează efectele stimulării receptorilor AT1 (36-39). În creier sunt prezenţi receptori AT2 atât în sistemul vascular, cât şi în talamus, hipotalamus, nucleii bazali.(40,41) Utilizarea în tratamentul hipertensiunii arteriale a inhibitorilor de enzimă de conversie a angiotensinei (ACEI) determină reducerea remodelării vasculare hipertensive, reducerea hipertrofiei ventriculare stângi, toate aceste fenomene fiind corelate cu creşterea tensiunii arteriale. Influenţează direct relaxarea şi complianţa miocardică prin scăderea depunerii colagenului interstiţial şi a fibrozei, procese mediate de angiotensină.(42,43)
3 Figura nr. 3. Sistemul renină-angiotensină-aldosteron O metaanaliză a 109 studii a găsit ACEI drept cele mai eficiente în reducerea hipertrofiei ventriculare stângi.(44) Tratamentul cu blocanţi de receptori de angiotensină II( BRA), antagonişti ai receptorilor AT1, determină inhibiţia efectului vasoconstrictor direct al angiotensinei II, prezervând efectul vasodilatator mediat de receptorii AT2. Studiul LIFE (Losartan Intervention for End Point reduction in hypertension) subliniază efectul neuroprotector al blocanţilor de receptori de angiotensină II independent de cel al reducerii tensiunii arteriale. În urma administrării de Losartan are loc o creştere a densităţii vaselor mici corticale, o reducere a agregării plachetare şi o scădere a concentraţiei de acid uric, cunoscut fiind faptul ca o agregabilitate plachetară crescută corelată cu un nivel ridicat de acid uric sunt asociate cu complicaţii majore cardiovasculare şi cerebrale.(45-48) Figura nr. 4. Tratamentul farmacologic al hipertensiunii În majoritatea studiilor, reducerea riscului de a dezvolta un accident este în concordanţă cu reducerea valorilor tensiunii arteriale. O reducere a tensiunii arteriale cu 10 mmhg duce la o reducere cu 20% până la 30% a riscului de accident vascular cerebral, aceasta când se fac comparaţii între grupe de pacienţi trataţi placebo şi cu medicamente antihipertensive.(49) Tabelul nr. 1. Incidenţa accidentului rezultată din trialuri clinice prospective, randomizate utilizând ca medicaţie inhibitorii de enzimă de conversie şi blocanţii de receptori de angiotensină II Studiul Patologia subiecţilor Timpul Numărul de de urmărire pacienţi (in ani) Tratament Incidenţa accidentului vascular cerebral (%) PROGRESS După accident Perindopril vs. Placebo 5.0% scădere CAPP Hipertensivi Captopril vs. 25% creştere Diuretice, beta-blocante ALLHAT Hipertensivi Lisinopril vs. 15% creştere chlorthalidone ANBP 2 Hipertensivi Enalapril vs. HCTZ Nici o schimbare HOPE Majoritatea normotensivi Ramipril vs. Placebo 32% scădere DIABHYCAR Diabetici cu microalbuminurie Ramipril vs. Placebo Nici o schimbare LIFE Hipertensivi cu Losartan vs. 25% scădere HVS Atenolol LIFE-ISH Hipertensivi Losartan vs. 40% scădere Atenolol SCOPE Hipertensivi 28% scădere SCOPE-ISH Hipertensivi Candesartan vs. medicamente convenţionale Candesartan vs. medicamente convenţionale ACCESS- PILOT După accident Candesartan vs. Placebo VALUE Cu risc mare Valsartan vs. hipertensiv Amlodipine Notă: Cercetări realizate în cadrul Proiectului POSDRU/88/1.5/S/60370 cofinanţat din Fondul Social European prin Programul Operaţional Sectorial Dezvoltarea Resurselor Umane REFERINŢE 1. Dahlöf B, Devereux RB, Kjeldsen SE, et al, LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359: Lithell H, Hansson L, Skoog I, et al. SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003;21: Schiffrin EL. Progress in secondary prevention of stroke with PROGRESS. The Perindopril Protection Against Recurrent Stroke study. Curr Hypertens Rep. 2002;4: Mancia G, De Backer G, Dominiczak A, et al guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the EuropeanSociety of Cardiology (ESC), Journal of Hypertension. 2007;25(6): Goldstein LB, Bushnell CD, Adamsetal RJ. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association, Stroke. 2010;42: % scădere 52% scădere 25% scădere AMT, vol. II, nr. 3, 2013, pag. 162
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